Impact of fetal inflammatory response on brain MRI abnormalities in extremely preterm infants

Neonates with fetal inflammatory response (FIR) are at increased risk of early-onset sepsis and death. We aimed to determine whether FIR and its severity are associated with brain abnormalities on MRI at term-equivalent age in extremely preterm infants.

A prospective cohort study of extremely preterm infants born between 2018 to 2021 with MRI scans completed at term equivalent age. Brain injury was assessed using the Kidokoro scoring, with MRIs independently scored by two blinded readers and adjudicated by a third. FIR severity was classified per the Amsterdam Placental Workshop Group Consensus Statement.

Among 141 infants, FIR was present in 59 (42%), with 46 (78%) having severe FIR ( ≥ stage 2). FIR was significantly associated with abnormal Kidokoro scores (P < 0.01), specifically white matter (P < 0.01) and cerebellar abnormalities (P = 0.01), but not cortical or deep gray matter abnormalities. Increasing FIR severity correlated with worse Kidokoro scores in both white and gray matter (P < 0.01). Other placental lesions showed no significant association. Inter-rater reliability was high (intraclass correlation coefficient >0.7).

This study is the first to link FIR severity to MRI brain abnormalities in extremely preterm infants, highlighting FIR as a risk factor for brain injury and delayed maturation.

Fetal Inflammatory Response (FIR) is associated with white matter and cerebellar injury by term-equivalent gestational age (TEA). There is significant relationship between severity and progression of FIR and brain abnormalities by TEA. This is the first study demonstrating the impact of progression and severity of FIR on abnormalities on MRI brain at term-equivalent gestational age. These observations provide additional insight into understanding the impact of intrauterine exposure to inflammation on the brain injury in extremely preterm infants.